- Email: [email protected]
Left Atrial Appendage Closure
JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 10, NO. 21, 2017
ª 2017 PUBLISHED BY ELSEVIER ON BEHALF OF THE
ISSN 1936-8798/$36.00
AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
http://dx.doi.org/10.1016/j.jcin.2017.07.028
EDITORIAL COMMENT
Left Atrial Appendage Closure Continuous Progress With Remaining Challenges* Horst Sievert, MD, Stefan Bertog, MD
R
andomized
atrial
stroke rate compared with warfarin) (2). Apart from
appendage closure (LAAC) to vitamin K an-
trials
comparing
left
efficacy, it is the safety events, residual leaks, and
tagonists (VKA) demonstrated at least equiv-
thrombus formation that must remain our focus.
alency in the prevention of all-cause strokes and
Experience with the procedure and a number of im-
superiority with respect to cardiovascular mortality
provements in the device and delivery system of the
and disabling strokes (1–3). Why then do we need
Watchman device (Boston Scientific, Natick, Massa-
further improvements of available technology? First,
chusetts) have led to a reduction in safety events
in the largest randomized trial to date comparing
compared to those reported in the PROTECT-AF and
LAAC to VKA, the PROTECT-AF (WATCHMAN Left
PREVAIL trials. This was recently demonstrated by
Atrial Appendage System for Embolic Protection in
the U.S. and European registries (5,6). Likewise, a
Patients With Atrial Fibrillation) trial, it required a
low number of safety events was reported in the
mean follow-up of 3.8 years to show equivalency in
Amplatzer Cardiac Plug (ACP) (St. Jude Medical, St.
the rate of safety events (2). Second, and perhaps sur-
Paul, Minnesota) multicenter registry (7). The results
prising to many, it must be emphasized that analysis of the PROTECT-AF trial and PREVAIL (Evaluation
SEE PAGE 2188
of the WATCHMAN LAA Closure Device in Patients
of the prospective, multicenter LAmbre (LifeTech
With Atrial Fibrillation Versus Long Term Warfarin
Scientific, Shenzhen, China) clinical study reported
Therapy), the second randomized trial, did not show
in this issue of JACC: Cardiovascular Interventions
a difference in all-cause major bleeding (4). This
by Huang et al. (8) suggests efficacy when thrombo-
was related to periprocedural safety events, particu-
embolic event rates after LAAC were compared with
larly, pericardial bleeding, that counterbalanced the
the expected event rate based on CHA2DS 2-VASc
higher post-procedural bleeding rate in the warfarin
scores in a historical control group without anticoa-
group. Fortunately, for those of us who recognize
gulation (8). Though reassuring, regulatory processes
the utility of LACC, the PROTECT-AF trial (after the
in some countries will likely require confirmation in a
less convincing results of the PREVAIL trial [3]), at
randomized trial before approval for commercial use.
long-term follow-up, did finally show a benefit in
One may argue about ethical concerns regarding
all-cause mortality (driven by the lower hemorrhagic
randomization of individuals with atrial fibrillation to LAAC or aspirin/no treatment in those who are at prohibitive risk of bleeding from oral anticoagulation, or perhaps, warfarin in those whose bleeding risk is
*Editorials published in JACC: Cardiovascular Interventions reflect the
low, because data have now convincingly shown a
views of the authors and do not necessarily represent the views of JACC:
benefit with LAAC compared with warfarin (1,2).
Cardiovascular Interventions or the American College of Cardiology. From the CardioVascular Center Frankfurt, Frankfurt, Germany. Dr. Sievert has received consulting fees, reimbursement for travel expenses or study honoraria from Abbott, Ablative Solutions, Ancona Heart,
Hence, the next step could be a randomized noninferiority trial comparing the LAmbre device to the Watchman device, or a randomized trial comparing it
Bioventrix, Boston Scientific, Carag, Cardiac Dimensions, Celonova, Cibiem,
to direct oral anticoagulation with prothrombin or fac-
CGuard, Comed B.V., Contego, CVRx, Edwards Lifesciences, Gardia, Hemo-
tor Xa inhibitors. There is an important aspect that
teq, InspireMD, Kona Medical, Lifetech, Maquet Getinge Group, Medtronic,
stands out. Although peridevice leaks are common
Occlutech, pfm Medical, Recor, St. Jude Medical, Terumo, Trivascular, Vascular Dynamics, Venus, and Veryan. Dr. Bertog has reported that he has
with the Watchman device, with incidences ranging
no relationships relevant to the contents of this paper to disclose.
between 32% (9) and 64% (10), depending on imaging
2196
Sievert and Bertog
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 21, 2017 NOVEMBER 13, 2017:2195–7
LAA Closure With Continuous Progress
modality, any peridevice leak was demonstrated in
in the EWOLUTION (Registry on Watchman Outcomes
only 16% after LAmbre implantation and leaks
in Real-Life Utilization) registry, in 93% of patients,
>3 mm in only 0.7% (8). This may be related to the
only 1 device was used, and most devices (71%) were
large diameter of the cover compared with the um-
implanted at first attempt (5). With the LAmbre device,
brella and/or the articulating waist allowing favorable
success was 88% with the first device, and successful
alignment of the cover with the appendage ostium. In
implant occurred in 57% at first attempt (8). The inci-
this context, a peridevice leak was reported in 12%
dence
with the ACP (7), a device with similar design features
(1.3%) (8) that may cause the event (stroke) that we
of
device-associated
thrombus
formation
including a larger disc size compared with the anchor
are trying to prevent, potentially diminishing efficacy
accommodating the challenging usually elliptical
of LAAC, was slightly lower than reported with other
shape of the appendage ostium. Alternatively, the
devices, 4.2% in the PROTECT-AF trial and the CAP
observed lower leak incidence may be related to
(Continued Access Protocol) registry (12), 3.7% in the
the definition of peridevice leak. In devices with a
EWOLUTION registry using the Watchman device
“pacifier” design in which an anchor securing the de-
(11), and 3.2% in the ACP multicenter study (7). Lastly,
vice is attached to a disc that seals the appendage
whereas device embolization, a potentially life-
ostium (i.e., LAmbre or ACP), leaks around the anchor
threatening event, was reported in 0.6% in the
may be rare. However, potentially unaccounted for
PROTECT-AF trial (13), 0.2% in the EWOLUTION regis-
leaks between the disc and anchor could be more com-
try (5), and 0.8% in the ACP multicenter registry (7), it
mon, and it remains to be determined whether this is
did not occur with the LAmbre device (though numbers
less consequential than peridevice leaks described
are too small to draw any final conclusions) (8).
with other devices. Therefore, the low leak rate may
In conclusion, although with LAAC, we have a
be a reflection of the definition rather than device
better alternative to oral anticoagulation with VKA for
design. Furthermore, leak or thrombus detection and
stroke prevention in patients with atrial fibrillation,
quantification between the disc and anchor is more
challenges remain regarding procedural safety, peri-
challenging than surrounding other devices such as
device leak, thrombus formation, and device embo-
the Watchman occluder. It would be important for
lization. In a procedure with the goal to prevent an
any future studies to clarify how peridevice leak is
event, the annual likelihood of which is relatively
defined other than merely by size (i.e., whether or
low, it is our responsibility to further improve device
not it includes leaks between the disc and anchor).
technology to achieve a procedural risk close to zero.
Though the clinical significance of peridevice leaks re-
In
mains unclear and some data support the assumption
study (8), technical success and ease of use were
the
prospective
multicenter
LAmbre
device
that small leaks are benign (10), the aim should be to
similar to the 2 other most frequently used LAAC
achieve as complete an occlusion as possible. The
devices,
high procedural success rate (99.4%) (8) is similar to
low. Likewise, the incidence of peridevice leak and
that reported in the latest European and U.S.
device-associated thrombus formation were very low.
Watchman
(98.5%,
Further, larger studies will be needed to confirm at
95.6%, and 97.3%, respectively) (6,7,11). Likewise,
least equivalency to the Watchman device or direct
ease of use, measured by number of devices tried at
oral anticoagulants or superiority to VKA.
and
ACP
multicenter
study
and
periprocedural
complications
were
implant and number of times a device required recapturing, an important aspect that impacts procedural
ADDRESS
safety, appears to be comparable to the Watchman de-
Horst Sievert, Cardiovascular Center, Seckbacher
FOR
CORRESPONDENCE:
vice and ACP. In the ACP multicenter study, in 93%,
Landstrasse 65, Frankfurt 60389, Germany. E-mail:
the first ACP tried was the final implanted device (7);
[email protected].
Prof.
Dr.
REFERENCES 1. Holmes DR Jr., Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol 2015;65:2614–23.
3. Holmes DR Jr., Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1–12.
2. Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA 2014;312:1988–98.
4. Price MJ, Reddy VY, Valderrabano M, et al. Bleeding outcomes after left atrial appendage closure compared with long-term warfarin: a pooled, patient-level analysis of the WATCHMAN
randomized trial experience. J Am Coll Cardiol Intv 2015;8:1925–32. 5. Boersma LV, Schmidt B, Betts TR, et al. Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION registry. Eur Heart J 2016;37:2465–74. 6. Reddy VY, Gibson DN, Kar S, et al. Postapproval U.S. experience with left atrial
Sievert and Bertog
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 21, 2017 NOVEMBER 13, 2017:2195–7
appendage closure for stroke prevention in atrial fibrillation. J Am Coll Cardiol 2017;69: 253–61. 7. Tzikas A, Shakir S, Gafoor S, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention 2016; 11:1170–9. 8. Huang H, Liu Y, Xu Y, et al. Percutaneous left atrial appendage closure with the LAmbre device for stroke prevention in atrial fibrillation: a prospective, multicenter clinical study. J Am Coll Cardiol Intv 2017;10:2188–94.
LAA Closure With Continuous Progress
(Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) substudy. J Am Coll Cardiol 2012;59:
12. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in
923–9.
Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011; 123:417–24.
10. Saw J, Tzikas A, Shakir S, et al. Incidence and clinical impact of device-associated thrombus and peri-device leak following left atrial appendage closure with the Amplatzer cardiac plug. J Am Coll Cardiol Intv 2017;10: 391–9.
9. Viles-Gonzalez JF, Kar S, Douglas P, et al. The clinical impact of incomplete left atrial appendage closure with the Watchman Device in
11. Boersma LV, Ince H, Kische S, et al. Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial. Heart
patients with atrial fibrillation: a PROTECT AF
Rhythm 2017;14:1302–8.
13. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009; 374:534–42.
KEY WORDS atrial fibrillation, left atrial appendage closure, stroke
2197
VOL. 10, NO. 21, 2017
ª 2017 PUBLISHED BY ELSEVIER ON BEHALF OF THE
ISSN 1936-8798/$36.00
AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
http://dx.doi.org/10.1016/j.jcin.2017.07.028
EDITORIAL COMMENT
Left Atrial Appendage Closure Continuous Progress With Remaining Challenges* Horst Sievert, MD, Stefan Bertog, MD
R
andomized
atrial
stroke rate compared with warfarin) (2). Apart from
appendage closure (LAAC) to vitamin K an-
trials
comparing
left
efficacy, it is the safety events, residual leaks, and
tagonists (VKA) demonstrated at least equiv-
thrombus formation that must remain our focus.
alency in the prevention of all-cause strokes and
Experience with the procedure and a number of im-
superiority with respect to cardiovascular mortality
provements in the device and delivery system of the
and disabling strokes (1–3). Why then do we need
Watchman device (Boston Scientific, Natick, Massa-
further improvements of available technology? First,
chusetts) have led to a reduction in safety events
in the largest randomized trial to date comparing
compared to those reported in the PROTECT-AF and
LAAC to VKA, the PROTECT-AF (WATCHMAN Left
PREVAIL trials. This was recently demonstrated by
Atrial Appendage System for Embolic Protection in
the U.S. and European registries (5,6). Likewise, a
Patients With Atrial Fibrillation) trial, it required a
low number of safety events was reported in the
mean follow-up of 3.8 years to show equivalency in
Amplatzer Cardiac Plug (ACP) (St. Jude Medical, St.
the rate of safety events (2). Second, and perhaps sur-
Paul, Minnesota) multicenter registry (7). The results
prising to many, it must be emphasized that analysis of the PROTECT-AF trial and PREVAIL (Evaluation
SEE PAGE 2188
of the WATCHMAN LAA Closure Device in Patients
of the prospective, multicenter LAmbre (LifeTech
With Atrial Fibrillation Versus Long Term Warfarin
Scientific, Shenzhen, China) clinical study reported
Therapy), the second randomized trial, did not show
in this issue of JACC: Cardiovascular Interventions
a difference in all-cause major bleeding (4). This
by Huang et al. (8) suggests efficacy when thrombo-
was related to periprocedural safety events, particu-
embolic event rates after LAAC were compared with
larly, pericardial bleeding, that counterbalanced the
the expected event rate based on CHA2DS 2-VASc
higher post-procedural bleeding rate in the warfarin
scores in a historical control group without anticoa-
group. Fortunately, for those of us who recognize
gulation (8). Though reassuring, regulatory processes
the utility of LACC, the PROTECT-AF trial (after the
in some countries will likely require confirmation in a
less convincing results of the PREVAIL trial [3]), at
randomized trial before approval for commercial use.
long-term follow-up, did finally show a benefit in
One may argue about ethical concerns regarding
all-cause mortality (driven by the lower hemorrhagic
randomization of individuals with atrial fibrillation to LAAC or aspirin/no treatment in those who are at prohibitive risk of bleeding from oral anticoagulation, or perhaps, warfarin in those whose bleeding risk is
*Editorials published in JACC: Cardiovascular Interventions reflect the
low, because data have now convincingly shown a
views of the authors and do not necessarily represent the views of JACC:
benefit with LAAC compared with warfarin (1,2).
Cardiovascular Interventions or the American College of Cardiology. From the CardioVascular Center Frankfurt, Frankfurt, Germany. Dr. Sievert has received consulting fees, reimbursement for travel expenses or study honoraria from Abbott, Ablative Solutions, Ancona Heart,
Hence, the next step could be a randomized noninferiority trial comparing the LAmbre device to the Watchman device, or a randomized trial comparing it
Bioventrix, Boston Scientific, Carag, Cardiac Dimensions, Celonova, Cibiem,
to direct oral anticoagulation with prothrombin or fac-
CGuard, Comed B.V., Contego, CVRx, Edwards Lifesciences, Gardia, Hemo-
tor Xa inhibitors. There is an important aspect that
teq, InspireMD, Kona Medical, Lifetech, Maquet Getinge Group, Medtronic,
stands out. Although peridevice leaks are common
Occlutech, pfm Medical, Recor, St. Jude Medical, Terumo, Trivascular, Vascular Dynamics, Venus, and Veryan. Dr. Bertog has reported that he has
with the Watchman device, with incidences ranging
no relationships relevant to the contents of this paper to disclose.
between 32% (9) and 64% (10), depending on imaging
2196
Sievert and Bertog
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 21, 2017 NOVEMBER 13, 2017:2195–7
LAA Closure With Continuous Progress
modality, any peridevice leak was demonstrated in
in the EWOLUTION (Registry on Watchman Outcomes
only 16% after LAmbre implantation and leaks
in Real-Life Utilization) registry, in 93% of patients,
>3 mm in only 0.7% (8). This may be related to the
only 1 device was used, and most devices (71%) were
large diameter of the cover compared with the um-
implanted at first attempt (5). With the LAmbre device,
brella and/or the articulating waist allowing favorable
success was 88% with the first device, and successful
alignment of the cover with the appendage ostium. In
implant occurred in 57% at first attempt (8). The inci-
this context, a peridevice leak was reported in 12%
dence
with the ACP (7), a device with similar design features
(1.3%) (8) that may cause the event (stroke) that we
of
device-associated
thrombus
formation
including a larger disc size compared with the anchor
are trying to prevent, potentially diminishing efficacy
accommodating the challenging usually elliptical
of LAAC, was slightly lower than reported with other
shape of the appendage ostium. Alternatively, the
devices, 4.2% in the PROTECT-AF trial and the CAP
observed lower leak incidence may be related to
(Continued Access Protocol) registry (12), 3.7% in the
the definition of peridevice leak. In devices with a
EWOLUTION registry using the Watchman device
“pacifier” design in which an anchor securing the de-
(11), and 3.2% in the ACP multicenter study (7). Lastly,
vice is attached to a disc that seals the appendage
whereas device embolization, a potentially life-
ostium (i.e., LAmbre or ACP), leaks around the anchor
threatening event, was reported in 0.6% in the
may be rare. However, potentially unaccounted for
PROTECT-AF trial (13), 0.2% in the EWOLUTION regis-
leaks between the disc and anchor could be more com-
try (5), and 0.8% in the ACP multicenter registry (7), it
mon, and it remains to be determined whether this is
did not occur with the LAmbre device (though numbers
less consequential than peridevice leaks described
are too small to draw any final conclusions) (8).
with other devices. Therefore, the low leak rate may
In conclusion, although with LAAC, we have a
be a reflection of the definition rather than device
better alternative to oral anticoagulation with VKA for
design. Furthermore, leak or thrombus detection and
stroke prevention in patients with atrial fibrillation,
quantification between the disc and anchor is more
challenges remain regarding procedural safety, peri-
challenging than surrounding other devices such as
device leak, thrombus formation, and device embo-
the Watchman occluder. It would be important for
lization. In a procedure with the goal to prevent an
any future studies to clarify how peridevice leak is
event, the annual likelihood of which is relatively
defined other than merely by size (i.e., whether or
low, it is our responsibility to further improve device
not it includes leaks between the disc and anchor).
technology to achieve a procedural risk close to zero.
Though the clinical significance of peridevice leaks re-
In
mains unclear and some data support the assumption
study (8), technical success and ease of use were
the
prospective
multicenter
LAmbre
device
that small leaks are benign (10), the aim should be to
similar to the 2 other most frequently used LAAC
achieve as complete an occlusion as possible. The
devices,
high procedural success rate (99.4%) (8) is similar to
low. Likewise, the incidence of peridevice leak and
that reported in the latest European and U.S.
device-associated thrombus formation were very low.
Watchman
(98.5%,
Further, larger studies will be needed to confirm at
95.6%, and 97.3%, respectively) (6,7,11). Likewise,
least equivalency to the Watchman device or direct
ease of use, measured by number of devices tried at
oral anticoagulants or superiority to VKA.
and
ACP
multicenter
study
and
periprocedural
complications
were
implant and number of times a device required recapturing, an important aspect that impacts procedural
ADDRESS
safety, appears to be comparable to the Watchman de-
Horst Sievert, Cardiovascular Center, Seckbacher
FOR
CORRESPONDENCE:
vice and ACP. In the ACP multicenter study, in 93%,
Landstrasse 65, Frankfurt 60389, Germany. E-mail:
the first ACP tried was the final implanted device (7);
[email protected].
Prof.
Dr.
REFERENCES 1. Holmes DR Jr., Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol 2015;65:2614–23.
3. Holmes DR Jr., Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1–12.
2. Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA 2014;312:1988–98.
4. Price MJ, Reddy VY, Valderrabano M, et al. Bleeding outcomes after left atrial appendage closure compared with long-term warfarin: a pooled, patient-level analysis of the WATCHMAN
randomized trial experience. J Am Coll Cardiol Intv 2015;8:1925–32. 5. Boersma LV, Schmidt B, Betts TR, et al. Implant success and safety of left atrial appendage closure with the WATCHMAN device: peri-procedural outcomes from the EWOLUTION registry. Eur Heart J 2016;37:2465–74. 6. Reddy VY, Gibson DN, Kar S, et al. Postapproval U.S. experience with left atrial
Sievert and Bertog
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 21, 2017 NOVEMBER 13, 2017:2195–7
appendage closure for stroke prevention in atrial fibrillation. J Am Coll Cardiol 2017;69: 253–61. 7. Tzikas A, Shakir S, Gafoor S, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention 2016; 11:1170–9. 8. Huang H, Liu Y, Xu Y, et al. Percutaneous left atrial appendage closure with the LAmbre device for stroke prevention in atrial fibrillation: a prospective, multicenter clinical study. J Am Coll Cardiol Intv 2017;10:2188–94.
LAA Closure With Continuous Progress
(Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) substudy. J Am Coll Cardiol 2012;59:
12. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in
923–9.
Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 2011; 123:417–24.
10. Saw J, Tzikas A, Shakir S, et al. Incidence and clinical impact of device-associated thrombus and peri-device leak following left atrial appendage closure with the Amplatzer cardiac plug. J Am Coll Cardiol Intv 2017;10: 391–9.
9. Viles-Gonzalez JF, Kar S, Douglas P, et al. The clinical impact of incomplete left atrial appendage closure with the Watchman Device in
11. Boersma LV, Ince H, Kische S, et al. Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial. Heart
patients with atrial fibrillation: a PROTECT AF
Rhythm 2017;14:1302–8.
13. Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009; 374:534–42.
KEY WORDS atrial fibrillation, left atrial appendage closure, stroke
2197